代谢酶NAT2多态性与大肠息肉及腺瘤的复发

N-actyltransferase2 polymorphism in recurrence of colorectal polyps and adenomas

目的 研究代谢酶基因NAT2多态性与大肠息肉及腺瘤复发的关系 ,探讨其与大肠癌遗传易感性。方法 在 1980年 ,建立了 40 76例大肠癌高危人群队列 ,这 40 76例均有大肠腺瘤或息肉史。从高危人群中随机抽取 5 2例息肉、腺瘤复发 2次以上者为复发组 ,另抽取 5 2例无复发者为对照 ,从抗凝外周血白细胞中提取DNA ,采用聚合酶链反应 限制性内切酶片段长度多态性 (PCR RFLP)方法分析 ,比较NAT2的多态性分布差异。结果 NAT2野生型Wt/Wt频率在无复发组 (17/ 5 2 ,32 7% )明显高于复发组 (8/ 5 2 ,15 .4% ) ,杂合型在复发组频率为 40 / 5 2 (76 .9% ) ,与无复发组频率30 / 5 2 (5 7.7% )比较 ,差异均有显著意义 (P <0 .0 5 )。以Wt/Wt基因型的危险度 (OR)为 1,则Wt/M 基因型的OR为 2 .96 ,95 %CI为 1.0 91～ 8.0 0 9,M /M 基因型的OR为 2 .12 5 ,95 %CI为 0 .6 6 6～6 781。在复发与无复发组中 ,未发现NAT2快速与慢速酶的差异。结论 NAT2野生型 (Wt/Wt)可能是大肠腺瘤复发的保护因素 。

Objective To observe the polymorphism of metabolizing enzyme N-ac t yltransferase 2 gene in populations with history of colorectal adenoma and polyp and to explore the relationship between NAT2 gene phenotype and colorectal canc er genetic susceptibility. Methods A cohort of 4 076 patients with history of co lorectal adenoma or polyp was established Fifty-two cases were randomly selecte d from those with recurrence more than 2 times during the twenty years' follow-u p . Fifty-two without recurrence were randomly selected as controls. DNA was isol a ted from the lymphocytes of peripheral blood of these 104 subjects. NAT2 polymor phism was detected by PCR-RFLP. Results The frequency of wild-type NAT2 (Wt/Wt) was significantly higher in control group (17/52, 32.7%) than in recurrence gro up (8/52, 15.4%) ( P <0.05). The frequency of heterogeneity type of NAT2 was s ignif icantly higher in recurrence group (40/52, 76.9%) than in control group (30/52, 57.7%) ( P <0.05). If OR of wild-type NAT2 (Wt/Wt) was 1, OR of Wt/M* g enotype was 2.96 (95%CI: 1.091～8 009), and OR of M*/M* genotype was 2.125 (95%CI: 0.666～6.7 81). There was no difference of distribution between rapid enzyme type and slow enzyme type in the two groups. Conclusion The frequency of wild-type NAT2 gen e (Wt/Wt) is significantly higher in patients without recurrence of adenoma or po lyp than in patients with recurrence. The frequency of heterogeneity genotype of NAT2 is significantly higher in patients with recurrence of adenoma or polyp th an in those without recurrence. Wild-genotype (Wt/Wt) may be a protection facto r in recurrence of colorectal adenomas. No difference can be seen between the dis tribution of rapid and slow enzyme types in these two groups.